Homozygous CDA*3 is a major cause of life-threatening toxicities in gemcitabine-treated Japanese cancer patients

H Ueno; N Kaniwa; T Okusaka; M Ikeda; C Morizane; S Kondo; E Sugiyama; S R Kim; R Hasegawa; Y Saito; T Yoshida; N Saijo; J Sawada

doi:10.1038/sj.bjc.6604971

Homozygous CDA*3 is a major cause of life-threatening toxicities in gemcitabine-treated Japanese cancer patients

Br J Cancer. 2009 Mar 24;100(6):870-3. doi: 10.1038/sj.bjc.6604971.

Authors

H Ueno¹, N Kaniwa, T Okusaka, M Ikeda, C Morizane, S Kondo, E Sugiyama, S R Kim, R Hasegawa, Y Saito, T Yoshida, N Saijo, J Sawada

Affiliation

¹ Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. [email protected]

Abstract

Among 242 Japanese pancreatic cancer patients, three patients (1.2%) encountered life-threatening toxicities, including myelosuppression, after gemcitabine-based chemotherapies. Two of them carried homozygous CDA*3 (CDA208G>A [Ala70Thr]), and showed extremely low plasma cytidine deaminase activity and gemcitabine clearance. Our results suggest that homozygous *3 is a major factor causing gemcitabine-mediated severe adverse reactions among the Japanese population.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Antimetabolites, Antineoplastic / adverse effects*
Area Under Curve
Asian People / genetics*
Cytidine Deaminase / genetics*
Deoxycytidine / adverse effects
Deoxycytidine / analogs & derivatives*
Deoxycytidine / pharmacokinetics
Female
Gemcitabine
Humans
Male
Middle Aged
Pancreatic Neoplasms / drug therapy*
Polymorphism, Single Nucleotide*

Substances

Antimetabolites, Antineoplastic
Deoxycytidine
Cytidine Deaminase
Gemcitabine